Pathogenesis of Endocrine Disease in Animals

Endocrine diseases can arise from several causes. Hormones can be over- or under-produced, receptors can malfunction, and normal pathways for hormone removal may be disrupted. Clinical signs consistent with malfunction in an endocrine tissue may develop because of a problem originating in the source of the hormone itself or may be due to disruption in another location that is secondarily affecting hormone secretion or action.

In veterinary medicine, the most common types of endocrine disease are1) hormonal overproduction associated with either a tumor or hyperplastic tissue manufacturing excessive amounts of hormone, and 2) hormonal deficiency due to destruction of the endocrine tissue source. Common diseases associated with hormonal overproduction are hyperthyroidism in cats Hyperthyroidism in Animals Hyperthyroidism is characterized by hypermetabolism and high circulating thyroid hormone concentrations. Clinical features include weight loss despite a good appetite. Treatment depends on the... read more and hyperadrenocorticism Cushing Disease (Pituitary-dependent Hyperadrenocorticism) in Animals Cushing disease is hyperadrenocorticism caused by an ACTH-secreting tumor of the pituitary gland. Clinical signs include polyuria, polydipsia, alopecia, and muscle weakness. A low-dose dexamethasone... read more (Cushing disease) in dogs.

Often, the abnormal endocrine tissue not only overproduces hormone but also fails to respond normally to feedback signals, contributing to inappropriate release of hormone. Hormonal overproduction from an endocrine tissue can also result from stimulation arising from a secondary source; eg, renal disease can result in parathyroid hyperplasia and oversecretion of parathyroid hormone (PTH). Hyperphosphatemia Hyperphosphatemia in Animals Physiologically elevated serum and plasma phosphorus concentrations are seen in young and growing animals due to enhanced intestinal phosphorus uptake and decreased renal phosphorus excretion... read more occurs as a consequence of some types of renal disease. This leads to decreased formation of the active form of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol). In turn, low calcitriol concentrations contribute to low calcium levels in extracellular fluid, which act as a stimulus for PTH secretion. Nonendocrine tissues can produce and secrete hormones in sufficient amounts to cause clinical signs; eg, certain tumors (apocrine gland tumors of the anal sac in dogs, lymphoma) can manufacture PTH-related protein that can mimic PTH action, resulting in hypercalcemia (paraneoplastic syndrome Paraneoplastic Disorders of the Nervous System ).

Syndromes associated with deficient or absent hormone secretion also have multiple causes. Endocrine tissue destruction secondary to cell-mediated autoimmune attack is often believed to be the cause. Examples of endocrine hypofunction resulting from primary tissue loss include canine hypothyroidism Hypothyroidism in Animals Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as lethargy, weight gain, obesity, haircoat changes, and low serum thyroid hormone concentrations. Management... read more , type 1 diabetes mellitus Diabetes Mellitus in Dogs and Cats Diabetes mellitus is a common endocrine disease in dogs and cats, occurring in about 1 of every 300 patients. Clinical signs reflect hyperglycemia with resultant glycosuria. Diagnosis is made... read more , primary hypoparathyroidism Hypoparathyroidism in Dogs Hypoparathyroidism of various causes is primarily recognized in dogs and is characterized by insufficient PTH secretion by parathyroid glands. Deficiency of PTH results in an inability to adequately... read more , and primary hypoadrenocorticism Addison Disease Addison disease (hypoadrenocorticism) results from the lack of glucocorticoids, mineralocorticoids, or both. Isolated aldosterone insufficiency appears to be very rare, whereas isolated glucocorticoid... read more .

In early stages of tissue loss, compensatory mechanisms involving feedback pathways stimulate activity (hormone production) from the remaining tissue. For example, in primary hypoadrenocorticism Addison Disease Addison disease (hypoadrenocorticism) results from the lack of glucocorticoids, mineralocorticoids, or both. Isolated aldosterone insufficiency appears to be very rare, whereas isolated glucocorticoid... read more (Addison disease), secretion of pituitary adrenocorticotropic hormone (ACTH) increases as the adrenal cortex disappears. The increased trophic support results in full activation of the remaining tissue and often provides sufficient hormone secretion to delay signs of deficiency until tissue loss simply eliminates the hormonal source. Disorders resulting in clinical signs of endocrine hypoactivity may also occur due to disruption in tissues distant from the hormone source. Secondary hypothyroidism results from pituitary thyroid-stimulating hormone (TSH) insufficiency that reduces the stimulus needed at the thyroid for T₄ and T₃ production and secretion. Glucocorticoid therapy may cause atrophy of the cortisol-producing zones in the adrenal cortex. The exogenous steroid initiates negative feedback on the pituitary gland, suppressing ACTH secretion and leading to adrenal cortical atrophy. Another potential cause of endocrine hypofunction relates to tissue loss secondary to compressive and/or destructive growth of nonfunctional tumors.

Endocrine disease and related maladies also result from alterations in tissue responsiveness to hormones. An important example is type 2 or non-insulin-dependent diabetes mellitus Diabetes Mellitus in Dogs and Cats Diabetes mellitus is a common endocrine disease in dogs and cats, occurring in about 1 of every 300 patients. Clinical signs reflect hyperglycemia with resultant glycosuria. Diagnosis is made... read more , in which relative insensitivity to insulin is observed, often associated with obesity. Nephrogenic diabetes insipidus is due to renal insensitivity to the actions of vasopressin (antidiuretic hormone). The renal insensitivity to vasopressin in this syndrome may relate to congenital abnormalities in the vasopressin receptor but more often is secondary to other diseases (eg, pyometra Pyometra in Small Animals Pyometra is a hormonally mediated diestrual disorder characterized by cystic endometrial hyperplasia with secondary bacterial infection. Pyometra is reported primarily in older bitches (>5 yr... read more , hyperadrenocorticism Cushing Disease (Pituitary-dependent Hyperadrenocorticism) in Animals Cushing disease is hyperadrenocorticism caused by an ACTH-secreting tumor of the pituitary gland. Clinical signs include polyuria, polydipsia, alopecia, and muscle weakness. A low-dose dexamethasone... read more ) or abnormalities in ion concentrations (eg, hypokalemia, hypercalcemia).